Downregulation of thyroid hormone receptor subtype mRNA levels by retinoic acid in cultured cardiomyocytes.
The thyroid hormone receptors (TR) and the retinoic acid receptors share a high degree of homology and their signaling pathways interplay. Thyroid hormone (T3) is known to be associated with various pathological heart conditions. Retinoids are known to ameliorate symptoms in hyperthyroid patients. The aim of this study was to investigate if retinoic acid (RA) can have any effects on TR in cardiac cells and thus play a role in heart disease. Confluent AT-1 cardiomyocytes were treated with RA, T3 depleted medium and DITPA (a cardiotonic T3 analogue) for 48 hours. Solution hybridization for the determination of mRNA for TR alpha 1, alpha 1, beta 1 and beta 2 was performed. RA, T3 and DITPA significantly downregulated the alpha 1, beta 1 and beta 2. The T3 depleted medium did not affect the TR subtypes. The specificity of the solution hybridization method was tested by an RNase protection assay. In conclusion, RA downregulates TR in a similar way as T3 in cardiac cells, indicating a role for RA in thyroid associated heart disease.
Drvota
V
V
Karolinska Institute at Department of Cardiology, Huddinge University Hospital, Sweden.
D015342:DNA Probes / Q000737:chemistry; D004104:Diiodothyronines / Q000494:pharmacology; D015536:Down-Regulation / Q000502:physiology*; D006331:Heart Diseases; D006801:Humans; D009206:Myocardium / Q000378:metabolism*; D011422:Propionates / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000145:classification / Q000378:metabolism*; D014212:Tretinoin / Q000378:metabolism / Q000494:pharmacology*; D014284:Triiodothyronine / Q000172:deficiency / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D015342:DNA Probes; D004104:Diiodothyronines; D011422:Propionates; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; C082182:3,5-diiodothyropropionic acid; D014212:Tretinoin